Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K38/00—Medicinal preparations containing peptides
  • A61K38/01—Hydrolysed proteins; Derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P13/00—Drugs for disorders of the urinary system
  • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P13/00—Drugs for disorders of the urinary system
  • A61P13/12—Drugs for disorders of the urinary system of the kidneys
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P39/00—General protective or antinoxious agents
  • A61P39/02—Antidotes

Definitions

• the toxic kidney damage represents a significant side effect of the cytostatic therapy of malignant tumors, which at the same time excludes about a third of the patients from the therapy.
• further toxic damage to other organs, especially the bone marrow can occur if the renal elimination of the cytostatics or immunosuppressants is delayed.
• Efforts to reduce toxicity by increasing diuresis and / or renal urine flow do not prevent serious disorders of kidney function due to the administration of cystostatics or immunosuppressants.
• the renal deficiency often remains undetected clinically because the urinary substances in the blood only increase when the kidneys lose their function more radically.
• the aim of the invention is to create a medicament which prevents damage to the kidney when cytostatic treatment of malignant tumors and when immunosuppressive agents are administered by blocking the mechanism of action of nephrotoxicity.
• this object is achieved by the use of a mixture of L-amino acids which produces a modulation in the (protein) metabolism of the kidney cell, a mixture of glycine, alanine, serine, threonine, valine, leucine, isoleucine and Proline has proven to be suitable.
• a formulation of the intravenous mixture in 8% aqueous solution has proven to be particularly suitable.
• the mixture is preferably composed of 9-11 g / 1 glycine, 12-17 g / 1 alanine, 10-18 g / 1 serine, 2-5 g / 1 threonine, 5-10 g / 1 valine, 6-10 g / 1.
• the amino acids can be dissolved in 0.45% saline solution, whereby the chloride of the saline solution can be partially replaced by aspartate with pH equilibration.
• the mixture proposed here in the case of intravenous administration before the cytostatic treatment, causes toxic kidney damage caused by the cytostatic medication or when administering im- largely counteracts munsuppressiva.
• the mixture proposed here stabilizes the renal filtration function and promotes the energy production of the tube cell during the early phase of kidney damage by cytostatics and immunosuppressants. This cellular point of attack of the mixture prevents the cell function loss leading to irreversible damage to the kidney cell with subsequent cell death.
• the use proposed here is thus aimed at healthy kidneys who are at risk of kidney damage when treating another disease.
• the kidney is not intended to be fed with the mixture proposed here, since this is otherwise ensured.
• the exclusive toxicity block directed against toxic noxa minimizes the nitrogen load at the same time.
• the protection effect depends on the concentration ratio of the amino acids used.
• the proposed use of neutral L-amino acids for nephroprotective purposes is based on the modulation of intracellular autophagy in the kidney cell.
• the activation of the autophagy system by nephrotoxic effects is reversibly blocked if the described L-amino acid mixture is applied beforehand.
• the composition of the mixture is based on systematic studies on proximal tubular cells of the kidney.
• the advantage of using a mixture consisting of different neutral amino acids is that they have a maximum effect in the cell What is achieved is that the individual L-amino acids of the mixture pass through the cell membrane via various transport channels and collect intracellularly. An intact kidney cell function proved to be an essential prerequisite for a successful toxicity blockade.
• ITS Isolated proximal tubular segments
• the ITS were suspended in an albumin-containing (10%) wrestling medium to which glucose (Gluc) and amino acids (AS) were added as substrates.
• the leak rates of N-acetyl- ⁇ -D-glucosaminidase (NAG) observed in the reincubation period are assigned to the mitochondrial acceptor control index (ACI).
• Cisplatin-free incubated ITS served as controls during the test.
• Gluc 18 mM / 1
• Gluc + AS 10 mM / 1 glucose + total 8 mM / 1 GLY, ALA, SER, THR, VAL, LEU, ILE, PRO.
• kidney function measured. 12 patients each received either pretreatment with a nephroprotective amino acid mixture according to Table 2 (LSG II) or with a commercially available, conventional amino acid mixture (Table 3) (LSG I). x + SEM.
• tubular N-acetyl-ß-D-glucosaminidase, NAG, based on grams of creatinine in urine
• glomerular glomerular filtration rate

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• Chemical & Material Sciences (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Animal Behavior & Ethology (AREA)
• Pharmacology & Pharmacy (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• General Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Organic Chemistry (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Urology & Nephrology (AREA)
• Reproductive Health (AREA)
• Endocrinology (AREA)
• Toxicology (AREA)
• Immunology (AREA)
• Proteomics, Peptides & Aminoacids (AREA)
• Epidemiology (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Medicines Containing Material From Animals Or Micro-Organisms (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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• 1988
  • 1988-12-22 DE DE3843241A patent/DE3843241A1/de active Granted
• 1989
  • 1989-12-21 EP EP90900071A patent/EP0408691B1/de not_active Expired - Lifetime
  • 1989-12-21 AT AT90900071T patent/ATE110570T1/de not_active IP Right Cessation
  • 1989-12-21 WO PCT/DE1989/000780 patent/WO1990006769A1/de active IP Right Grant
  • 1989-12-21 ES ES90900071T patent/ES2063332T3/es not_active Expired - Lifetime
  • 1989-12-21 DE DE58908288T patent/DE58908288D1/de not_active Expired - Fee Related
  • 1989-12-21 RU SU894830956A patent/RU2077883C1/ru active
  • 1989-12-21 AU AU48079/90A patent/AU4807990A/en not_active Abandoned
  • 1989-12-21 JP JP2500961A patent/JPH078790B2/ja not_active Expired - Lifetime

Non-Patent Citations (3)

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